Pharmacophore modeling coupled with molecular dynamic simulation approach to identify new leads for meprin-β metalloprotease

Human meprin beta metalloprotease, a small subgroup of the astacin family, is a potent drug target for the treatment of several disorders such as fibrosis, neurodegenerative disease in particular Alzheimer and inflammatory bowel diseases. In this study, a ligand-based pharmacophore approach has been used for the selection of potentially active compounds to understand the inhibitory activities of meprin-β by using the sulfonamide scaffold based inhibitors. Using this dataset, a pharmacophore model (Hypo1) was selected on the basis of a highest correlation coefficient (0.959), lowest total cost (105.89) and lowest root mean square deviation (1.31 Å) values. All the pharmacophore hypotheses generated from the candidate inhibitors comprised four features: two hydrogen-bond acceptor, one hydrogen-bond donor and one zinc binder feature. The best validated pharmacophore model (Hypo1) was used for virtual screening of compounds from several databases. The selective hit compounds were filtered by drug likeness property, acceptable ADMET profile, molecular docking and DFT study. Molecular dynamic simulations with the final 10 hit compounds revealed that a large number of non-covalent interactions were formed with the active site and specificity sub-pockets of the meprin beta metalloprotease. This study assists in the development of the new lead molecules as well as gives a better understanding of their interaction with meprin-β.     

Coordination polymers of CdII and PbII with croconate show remarkable differences in coordination patterns: a structural and spectroscopic study

The croconate dianion is a highly versatile ligand with two tautomeric forms making it useful for building large superstructures in the solid state. The single‐crystal X‐ray structures of Pb^II– and Cd^II–croconate coordination polymers, namely catena‐poly[[[diaqualead(II)]‐μ‐croconato‐κ⁴O¹,O²:O³,O⁴] monohydrate], {[Pb(C₅O₅)(H₂O)₂]·H₂O}_n, 1 , and catena‐poly[[triaquacadmium(II)]‐μ‐croconato‐κ⁴O¹,O²:O³,O⁴], [Cd(C₅O₅)(H₂O)₃]_n, 2 , have been determined. Both polymers form one‐dimensional (1D) structures; 1 is a nonplanar 1D zigzag coordination polymer extended along the crystallographic b axis, whereas 2 is a planar 1D ribbon parallel to the [101] direction. In 2 , three H₂O molecules are coordinated directly to the metal atom, while in 1 , only two H₂O molecules are directly coordinated to the metal atom. A third interstitial H₂O molecule is involved in hydrogen bonding with O atoms of the croconate ligands of an adjacent layer and other H₂O molecules, resulting in stacked double layers parallel to the [105] plane. Solid‐state FT–IR and solution UV–Vis spectra also substantiate the croconate coordination.     

爆轰波对碰驱动下平面铅飞层对碰区动载行为实验研究

 采用高速光学照相和脉冲X光照相技术,对滑移爆轰波对碰驱动下平面铅飞层对碰区的动载行为进行了实验研究。实验结果显示,在爆轰波对碰区铅飞层出现了类似射流状超前凸起的现象,对碰区凸起呈现出速度和密度有明显差别的多层分区结构。凸起头部速度较高,运动过程中因自身的速度梯度及与周围空气的相互作用,呈现出明显的散碎、雾化特征,体密度远低于初始密度。凸起根部速度相对较低、密度较高,但随时间的推移仍迅速转变为非密实状态。对碰爆轰波的波剖面结构,以及材料的强度和冲击熔化可能是主导对碰区动载行为的主要因素。     

Correlations between Raman parameters and elemental composition in lead and lead alkali silicate glasses

This article examines the influence of the composition on the Raman spectra of lead silicate glass. Modern and historic lead alkali glasses and high‐lead glazed ceramics were analysed complementarily by Raman spectrometry and elemental techniques, either electron microprobe, proton induced X‐ray emission (PIXE) or scanning electron microscope with energy dispersive spectrometry (SEM‐EDS). The results showed that lead alkali silicate and high‐lead silicate glasses can be easily distinguished from their Raman spectra profile. In lead alkali silicate glasses, continuous variations were observed in the spectra with the compositional change. In particular, the position of the intense peak around 1070 cm⁻¹ was linearly correlated to the lead content in the glass. A unique decomposition model was developed for the spectra of lead alkali silicate glasses. From the combination of the Raman and elemental analyses, correlations were established between the spectral components and the composition. These correlations permitted to interpret the spectra and access additional compositional information, such as the lead content from area ratio A₉₉₀/A_900–1150, the total alkali + alkaline‐earth content from the area ratio A₁₁₀₀/A_900–1150 or the silica content from the area ratio A₁₁₅₀/A_900–1150. In lead silicate glass containing over 25 mol% PbO, the compositional variation induced no variation in the SiO₄ network region of the Raman spectra [150–1350 cm⁻¹], therefore no correlations and compositional information could be gained from the glass spectra in this range of composition. This new development of Raman spectroscopy for the analyses of glass will be very valuable for museums to not only access compositional information non‐destructively but also to understand the structural changes involved with their alteration. Copyright © 2008 John Wiley & Sons, Ltd.     

Possible relationship between Seismic Electric Signals (SES) lead time and earthquake stress drop

Stress drop values for fourteen large earthquakes with M(W)> or =5.4 which occurred in Greece during the period 1983-2007 are available. All these earthquakes were preceded by Seismic Electric Signals (SES). An attempt has been made to investigate possible correlation between their stress drop values and the corresponding SES lead times. For the stress drop, we considered the Brune stress drop, Deltasigma(B), estimated from far field body wave displacement source spectra and Deltasigma(SB) derived from the strong motion acceleration response spectra. The results show a relation may exist between Brune stress drop, Deltasigma(B), and lead time which implies that earthquakes with higher stress drop values are preceded by SES with shorter lead time.     

有界非局域非线性介质中空间光孤子传输的研究

对有界非局域非线性介质边界对孤子传输的影响进行了研究.基于非局域非线性薛定谔方程以及热传导的泊松方程,采用格林函数法求出了强非局域介质铅玻璃的响应函数和临界功率;从光线方程出发得到了偏离材料中心入射的光束中心振荡轨迹以及周期的解析解.通过数值模拟证明了该结果在不靠近样品边界的范围内都是准确的. 关键词： 空间光孤子 铅玻璃 非局域非线性     

Effect of surface morphology of lead dioxide particles on their ozone generating performance

Lead dioxide is widely applied in anodic oxidation processes like the ozone generation and the degradation of various organic species in aqueous solution. In this paper, the correlation between the morphology of the lead dioxide particles and their ozone generating performance was investigated. The anode prepared by crude lead dioxide particles exhibited better performance in ozone generation than that prepared by milled lead dioxide particles. The reason lies in, probably, the higher stability of O on the surfaces of the crude lead dioxide particles. With 220-h running of the anode prepared with crude lead dioxide particles, the overall diameters of the lead dioxide particle decreased drastically, and many nano-scaled lead dioxide particles presented on the surfaces of the particles, which had resulted from recrystallization of the particles at high potentials. The two facts might be the main reason for the decline of the membrane electrode performance. Furthermore, a small percentage of α-lead dioxide detected in lead dioxide crystal may also decline the performance of the membrane electrode.     

Calorimetric Investigations of the System Pb-Bi-Mg-Sb with Oelsen's Method

The results of calorimetric investigations in the section Pb-Bi_x-Mg_y-Sb_z (mole ratio Bi:Mg:Sb=8:1:1) of the system Pb-Bi-Mg-Sb with Oelsen's method are presented. The constructed space diagram and enthalpy isotherm diagram were used to determine integral mixing enthalpies for the investigated section in the temperature interval 450–1100 K. This revised version was published online in August 2006 with corrections to the Cover Date.     

Spectroscopic analysis and laser modeling of neodymium-doped potassium lead chloride

We present a discussion of the low-phonon energy host material potassium lead chloride, KPb₂Cl₅, doped with neodymium. Crystal growth, spectroscopic measurements, and an analysis of the magnetic and electric dipole transitions based on the Judd-Ofelt model are presented. Concentration quenching of the fluorescence is also examined. Based on the spectroscopic data and the known resonances in energy spacing of the first three excited states in neodymium, we suggest the possibility of a 3-for-1 cross-relaxation process. This process may efficiently populate the first excited state, ⁴I_11/2, which we show to be metastable with lifetime on the order of a few milliseconds. Population inversion of this level should be possible enabling a laser based on the 5.5-μm, ⁴I_11/2 to ⁴I_9/2 transition.